The antigenic variation is a clone phenotypical change developed by pathogenic microorganisms involving surface exposed antigenic determinants. These organisms use different mechanisms to change their surface antigen expression, thus being able to maintain a chronic infection under the continuous immune pressure generated by the host (Deitsch, K. W., Moxon, E. R. & Wellems, T. E. Microbiol. Mol. Biol. Rev. 61, 281-293 (1997)). Giardia lamblia (also runwayd Giardia intestinalis or Giardia duodenalis) is one of the most common human intestinal parasites. Protozoan G. lamblia also shows antigenic variation (Adam, R. D. Clin. Microbiol. Rev. 14, 447-475 (2001) and Nash, T. E. Phil. Trans. R. Soc. Lond. B 352, 1369-1375 (1997)), in a process that allows the parasite to develop chronic and/or recurrent infections. From a repertoire of about 190 genes codifying variable surface proteins (VSPs), Giardia only expresses one VSP on the surface of each parasite at a particular time, but spontaneously switches to a different VSP by an unknown mechanism. In Giardia, antigenic variation is responsible for the variable and/or persistent course of some infections, as well as the tendency to multiple infections, and involves a protein family known as VSPs (Adam, R. D. Clin. Microbiol. Rev. 14, 447-475 (2001) and Nash, T. E. Phil. Trans. R. Soc. Lond. B 352, 1369-1375 (1997).
VSPs line the complete trophozoite surface and are the main antigens recognized by the host immune response. VSPs range in size between 30 kDa and 200 kDa; they possess a variable cysteine-rich amino-terminal region and a conserved carboxy-terminal region that includes a hydrophobic transmembrane domain and a short cytosolic tail comprising only 5 amino acids (CRGKA (SEQ ID NO:145)). The parasite genome encodes a repertoire of ˜190 genes codifying VSPs (Morrison, H. G. et al. Science 317, 1921-1926 (2007), but only one VSP is expressed at any given time on the surface of each trophozoites. Switching to the expression of another VSP occurs once every 6-13 generations, even in the absence of any immunological pressure (Nash, T. E., Alling, D. W., Merritt, J. W. Jr & Conrad, J. T. Exp. Parasitol. 71, 415-421 (1990). Similarly to the rest of G. lamblia genes, the VSPs codifying genes have no introns and their upstream regions are relatively short and have been found to have limited or no sequence conservation. Moreover, there are no typical eukaryotic promoters present in these regions. The non-translated 3′ regions of messenger RNA including Giardia VSPs genes also tend to be short, typically 0-30 nucleotides long. So far, neither gene-rearrangement processes nor promoter-dependent switch-on/switch-off mechanisms have been demonstrated to be involved in Giardia's antigenic switching (Adam, R. D. Clin. Microbiol. Rev. 14, 447-475 (2001); Nash, T. E. Phil. Trans. R. Soc. Lond. B 352, 1369-1375 (1997) and Nash, T. E., Ailing, D. W., Merritt, J. W. Jr & Conrad, J. T. Exp. Parasitol. 71, 415-421 (1990).